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Tuberculosis, Multidrug-ResistantPhase 2StakeNCT05555303

Preventing Acquired Resistance: Strengthen TB Treatment by Adding Amikacin in the First Treatment Week of Multidrug-resistant Tuberculosis

A Phase 2 study testing Amikacin in people with Tuberculosis, Multidrug-Resistant, run by Rwanda Biomedical Centre at 1 site in Rwanda.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Acquired drug-resistance is a major challenge for tuberculosis (TB) care programs. The 2020 WHO guidelines recommends replacing second-line injectables by bedaquiline in rifampicin-resistant TB (RR-TB) treatment regimens. However, recent reports show too high rates of acquired bedaquiline resistance. Read more about this study

Who is it for?
Ages 19 to 64 years
Conditions the study is for
Tuberculosis, Multidrug-Resistant
What is being tested?
Amikacin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteRwanda
Study dates
1 Mar 2023to Feb 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Enrolled in the Master SHORRT study
  • Able and willing to provide written informed consent for the present substudy "Stake"
  • Is willing and able to give informed consent to be enrolled in the research project and for follow-up
  • Has bacteriologically or molecularly confirmed TB with evidence of resistance to at least rifampicin

Who cannot join

  • Any audiometry abnormality (grade 1 or higher) on baseline audiometry
  • History of kidney disease or baseline creatinine clearance below or equal to 60ml/min
  • Pregnant or breastfeeding women
  • History of previous injectable based tuberculosis treatment (including with streptomycin)
  • < 18 years and > 65 years old
  • Patient on NSAID or on diuretics
Show all 11Show fewer
  • Master ShORRT study
  • Is unable to take oral medication;
  • Must take any medications contraindicated with the medicines in the MDR/RR-TB regimen;
  • Has a known allergy to any of the drugs in the MDR/RR-TB regimen;
  • Has a QTcF interval of ≥ 500 msec; at baseline that does not correct with medical management.

Trial locations and contacts

1 site in 1 country.

Yves Habimana-Mucyo, MSc contact

+250733436765

yves.mucyo@rbc.gov.rw

Jean Claude S. NGABONZIZA, PhD contact

+250788740490

jclaude.ngabonziza@rbc.gov.rw

Rwanda1 site, 1 recruiting

  • Kabutare hospital

    Kabutare

    Yves Habimana-Mucyo, MSc, +250733436765, yves.mucyo@rbc.gov.rw

    Recruiting

Other trials in Rwanda

About this study

Official title: Preventing Acquired Resistance: Strengthen TB Treatment by Adding Amikacin in the First Treatment Week of Multidrug-resistant Tuberculosis (Stake) Amendment to Study Protocol: "All-oral Shorter Treatment Regimen for Multidrug- and Rifampicin-resistant Tuberculosis (MDR/RR-TB): Evaluating Its Effectiveness, Safety and Impact on the Quality of Life of Patients in Rwanda" (ShORRT)

Acquired drug-resistance is a major challenge for tuberculosis (TB) care programs. The 2020 WHO guidelines recommends replacing second-line injectables by bedaquiline in rifampicin-resistant TB (RR-TB) treatment regimens. However, recent reports show too high rates of acquired bedaquiline resistance. This may be explained by the delayed onset of action of bedaquiline. The investigators will study whether high-dose amikacin (a second-line injectable), administered during the first week of RR-TB treatment, is safe in 20 patients treated for RR-TB in Rwanda. If safe, further studies will assess whether adding amikacin in the first treatment week protect against acquired bedaquiline resistance. This study is embedded in an ongoing "Master study" of the ShORRT (short oral RR-TB) treatment regimen in Rwanda, a before/after study, with a retrospective cohort (before; the previously recommended second-line injectable-containing RR-TB regimen) and a prospective cohort (after: the newly recommended ShORRT regimen).

Being tested
Amikacin
Keywords
multidrug- and rifampicin-resistant tuberculosis
Medical subject headings
Tuberculosis, Multidrug-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AmikacinDrug

    In addition to the all-oral RR-TB treatment, add two intramuscular doses each consisting of 30 mg amikacin/kg, a first dose on day 1 and a second dose on day 4, all in the first week of treatment.

    The amikacin solution will be admixed with a lidocaine solution in the syringe before administration.

Study groups in NCT05555303
Study groupRoleWhat they receive
AmikacinOtherNot described
Receives: Drug: Amikacin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. grade 3-4 AE likely or definitively related to amikacin

    Assess whether less than 14% of patients treated with the amikacin-strengthened regimen will experience a grade 3-4 adverse event likely or definitively related to the use of amikacin

    Measured: After 2 weeks of treatment

Secondary outcomes (12)

  1. turnaround times

    Assess the turnaround times to inform the feasibility of doing the tests proposed in this study for the assessment of the response to the use of two doses of amikacin

    Measured: at the end of treatment week 2 (+/- 3 d)

  2. testing coverage

    Assess the testing coverage (proportion of patients with a result for each of the tests) to inform the feasibility of doing the tests proposed in this study for the assessment of the response to the use of two doses of amikacin

    Measured: at the end of treatment week 2 (+/- 3 d)

  3. AE likely or definitely related to amikacin

    Describe the occurrence of adverse events that are considered as likely or definitely related to the use of amikacin

    Measured: at the end of treatment week 2 (+/- 3 d)

  4. amikacin concentration

    Describe the amikacin concentration stratified by values for different treatment response markers : Colony forming units on semi-quantitative culture

    Measured: during the first two treatment weeks

  5. amikacin concentration

    Describe the amikacin concentration stratified by values for different treatment response markers : molecular bacterial load

    Measured: during the first two treatment weeks

  6. amikacin concentration

    Describe the amikacin concentration stratified by values for different treatment response markers : thin-layer agar semi-quantitative culture

    Measured: during the first two treatment weeks

  7. amikacin concentration

    Describe the amikacin concentration stratified by values for different treatment response markers: RNA Synthesis ratio

    Measured: during the first two treatment weeks

  8. amikacin concentration

    Describe the amikacin concentration stratified by values for different treatment response markers : time to culture positivity on liquid culture

    Measured: during the first two treatment weeks

  9. post-injection pain

    Describe post-injection pain on a 0-10 pain scale (The Wong-Baker FACES pain rating scale) (15)

    Measured: at 0, 15 minutes, 30 minutes and 60 minutes after the injection of amikacin with lidocaine on day 1 and 4, as well as the next morning

  10. all AE, relationship with TB drugs

    Describe all AE, by their grade, and their relationship with TB drugs

    Measured: at the end of the ShORRT study, approximately 23 months after the treatment

  11. treatment outcomes

    Describe treatment outcomes, using the following effectiveness endpoints:

    • Month of stable (without reversion) culture conversion
    • End-of-treatment outcomes (treatment failure, death during treatment, LTFU during treatment, cure, treatment completion)
    • Treatment outcomes at 12 months post-treatment (end-of treatment outcome corrected for relapse)
    • Acquired resistance to bedaquiline, fluoroquinolone, amikacin through target deep sequencing on paired baseline and failure sputa

    Measured: at the end of treatment

  12. post-treatment outcomes

    Describe post-treatment outcomes, using the following effectiveness endpoints:

    • Month of stable (without reversion) culture conversion
    • End-of-treatment outcomes (treatment failure, death during treatment, LTFU during treatment, cure, treatment completion)
    • Treatment outcomes at 12 months post-treatment (end-of treatment outcome corrected for relapse)
    • Acquired resistance to bedaquiline, fluoroquinolone, amikacin through target deep sequencing on paired baseline and failure sputa

    Measured: after post-treatment follow-up (part of ShORRT analysis)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Sep 2022
  2. Study start1 Mar 2023
  3. Primary completionMar 2024 (estimated)
  4. Study completionFeb 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05555303
Sponsor's protocol ID
RBC/RIDS012022
Acronym
Stake
Status last verified
Mar 2023
First submitted
16 Sep 2022
Last updated
29 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Snobre J, Gasana J, Ngabonziza JCS, Cuella-Martin I, Rigouts L, Jacobs BK, de Viron E, Herssens N, Ntihumby JB, Klibazayre A, Ndayishimiye C, Van Deun A, Affolabi D, Merle CS, Muvunyi C, Sturkenboom MGG, Migambi P, de Jong BC, Mucyo Y, Decroo T. Safety of high-dose amikacin in the first week of all-oral rifampicin-resistant tuberculosis treatment for the prevention of acquired resistance (STAKE): protocol for a single-arm clinical trial. BMJ Open. 2024 Jul 24;14(7):e078379. doi: 10.1136/bmjopen-2023-078379.

    PubMed 39053960

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Amikacin in people with Tuberculosis, Multidrug-Resistant, run by Rwanda Biomedical Centre at 1 site in Rwanda.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 29 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Rwanda. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Yves Habimana-Mucyo, MSc (+250733436765, yves.mucyo@rbc.gov.rw), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

grade 3-4 AE likely or definitively related to amikacin (time frame: After 2 weeks of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05555303, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2023.

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